The use of electricity in cosmetology and medicine are well-known: continuous or pulsed low voltage direct current (DC) being used for electrolytic therapy and/or deposition of substances in tissue and AC being used for cutting tissue.
Electrolytic treatments of tissue include, inter alia, use of the following procedures and definitions as used herein:
1. Electrophoresis: the movement of suspended particles through a fluid or gel under the action of an electromotive force applied to electrodes in contact with the suspension.
2. Iontophoresis: the introduction of an ionized substance (such as an active pharmaceutical ingredient) through intact skin by the application of a direct electric current.
3. Electroosmosis: the movement of a liquid out of or through a biological membrane under the influence of an electric field wherein non-charged solutes move along an electro-osmotically induced gradient.
4. Electrolytic desiccation: the removal of water from tissue using an electric current to move an electrolyte desiccant into the tissue.
5. Electokinesis: the motion of particles or liquids that results from or produces a difference of electric potential.
6. Electro-epilation: the use of electrical current to remove hair.
7. Electro-onychomycotomy: the use of electrical current to treat a fungus infection of the nail.
Electrolytic treatments are restricted to using low voltage DC because high voltage DC interferes with nerve and muscle activity, causing pain and tissue damage.
Low voltage DC, though, is an inefficient means of electrolytically affecting tissue, often resulting in deposition of insufficient amounts of a therapeutic substance in the tissue. Alternatively, to achieve sufficient deposition of the substance, low voltage DC requires a lengthy period of time that can be intolerable to a recipient while causing inefficient use of caregiver facilities.
Dispensing electrolytic treatment even using low voltage DC is not completely risk free. For example, low voltage DC electrophoresis that is inadvertently discharged near the heart may cause potentially fatal fibrillation of the ventricles. Additionally, since electrons do not travel in water, reactions at the tissue-electrode interface generally produce oxidation-reduction in substrates that are in contact with the electrodes, often resulting in tissue damage.
In spite of the drawbacks, including the inefficient and lengthy treatments, there are cosmetic treatments that currently use electrolytic DC, for example:
Hyperhydrosis
Primary hyperhydrosis, the overproduction of perspiration, occurs over various body surfaces, including palmar, axillary, plantar, facial, and truncal surfaces. Light to moderate hyperhydrosis is typically treated with applications of 25% aluminum chloride applications several times weekly. Hyperhydrosis that is recalcitrant to topical applications is often treated with iontophoresis.
Electrolytic treatments use devices that supply low DC voltage at 15-18 mA, thereby causing iontophoresis of a solution that typically include aluminum chloride. Treatments last 20-30 minutes each and are provided several times weekly. Resolution of symptoms and patient satisfaction vary considerably: many considering the treatments too time-consuming, inefficient, and/or expensive
There are two types of sweat glands, eccrine and apocrine. Eccrine sweat glands open to the skin, are under sympathetic cholinergic control, and respond to both thermal and psychological stimulus. Apocrine sweat glands, associated with mammalian sexual scent, are larger than eccrine glands, open to hair follicles, and innervated by sympathetic adrenergic nerve fibers. It is highly likely that eccrine glands respond to different electrical components of iontophoresis than apocrine glands. Not only would a treatment be dispensed more rapidly with a more efficient iontophoretic unit, but also better results could accrue with dual currents: a first for apocrine sweat glands, and a second for eccrine sweat glands.
Potential for Electrolytic Treatments
In addition to iontophoresis for treatment of hyperhydrosis, there are a number of cosmetic treatments that would potentially benefit from a more efficient and efficacious DC electrolytic apparatus.
Electro-Epilation
Referring to FIG. 1, a hair 204 grows from a follicle 208. As follicle 208 is an area where the hair shaft has not fully keratinized, follicle 208 rapidly absorbs electrolytic products.
The life cycle of follicle 208 is divided into 3 phases: anagen, catagen, and telogen. The anagen phase is the phase of active growth. The catagen phase marks regression of follicle 208, and the telogen phase represents a resting period. In the human scalp, the anagen phase lasts approximately 3-4 years. The catagen phase lasts approximately 2-3 weeks, and the telogen phase lasts approximately 3 months.
Onychomycosis
Onychomycosis is an infection that causes fingernails or toenails to thicken, discolor, disfigure, and/or split. Initially disfigurement is primarily a cosmetic concern, though without treatment, the nail can thicken, causing pressure, irritation, and pain in closed shoes.
In diabetics, onychomycosis is both common and dangerous; recent studies have shown a higher rate of amputation in diabetics with onychomycosis compared to those without the infection.
Onychomycosis is difficult to treat because nails grow slowly and receive very little blood supply. Onychomycosis pathogens generally comprise fungal and/or yeast: fungal pathogens including trichophyton rubrum and trichophyton mentagrophytes; and yeast pathogens including candida albicans and candida parapsilosis.
Topical antifungal medication requires 6 months to a year of daily treatments for the nail to regain a healthy, clear, thin appearance. Additionally, there is a relatively high rate of failure and recurrence following treatment.
A well-focused and deep electrolytic intracellular deposition of onychomycotic treatment agents would likely result in fewer treatments and less chance of recurrence.
Actinic Keratosis
Actinic keratosis is a scaly or crusty bump that forms on the skin surface on sun-exposed areas: face, ears, bald scalp, neck, backs of hands and forearms, and lips.
Actinic keratosis can be the first step in the development of skin cancer. It is estimated that up to 10 percent of active lesions, which are redder and tenderer than the rest, will take the next step and progress to squamous cell carcinoma.
The most aggressive form of keratosis, actinic cheilitis, appears on the lips and can evolve into squamous cell carcinoma. Roughly one-fifth of these chelitic-based carcinomas metastasize. More problematic, cancer in the presence of keratosis is not limited to squamous cell carcinoma, but may develop into a highly aggressive and metastatic melanoma.
Treatment is essential in order to avoid the potentially more invasive and extensive treatment of a subsequent malignancy. Current treatments of actinic keratosis include curettage, shave removal, cryosurgery chemical peels and topical creams, for example creams including 5-fluorouracil (5-FU). Each type of treatment is associated with varying initial success but a high rate of return several months to several years down the road.
Actinic keratosis treatment must reach the root of the keratosis in the skin basement membrane to be effective. One theory on why actinic keratosis returns following removal is that the above-noted treatments are not carried down to a sufficient depth due to fear of causing skin scarring. An electrolytic system that deposits medication in and below the basement membrane has greater potential to successfully treat actinic keratosis; without recurrence and without the trauma of ablation or cutting.
Inoperable Tumors
An example of a tumor that is rarely, if ever, surgically excised is a cancerous liver tumor. Surgical excision of liver cancer is not an option because during the surgery, leukemia cells associated with the cancer easily spread to all the organs via the blood stream and the lymph vessels.
There are two main kinds of liver cancer, hepatoma and cholangiocarcinoma. Hepatoma is cancer of the hepatocytes, the main functioning liver cell. Hepatoma is primary liver cancer. Hepatoma usually grows in the liver as a ball-like tumor, invading the normal tissue surrounding it. A history of infection with the hepatitis B virus puts individuals at risk of developing hepatoma.
Cholangiocarcinoma is cancer of the bile duct cells. Cholangiocarcinoma originates in the bile ducts and is often caused by infestation with liver fluke, a parasite called Clonorchis. The cancer grows along the bile ducts in sheets or lines, and is hard to find on X-ray studies.
Most cases of liver cancer are metastases from another organ. Because of its very high blood flow and many biological functions, the liver is one of the most common places for metastases to grow. Tumors that originally arise in the colon, pancreas, stomach, lung, or breast often spread to the liver.
Treatment of liver cancer varies according to the tumor size. Tumors less than 5 cm in diameter are often destroyed using ethanol or acetic acid injected into the tumor.
For tumors greater than 5 cm, a first line treatment for hepatic carcinoma is often chemotherapy where cytotoxic active pharmaceutical ingredients (APIs) are used to destroy cancer cells. APIs are usually given intravenously directly into the hepatic artery during each dhemotherapy session. A session typically lasts a few days, followed by recovery period from the side effects. The number of sessions depends on the type of liver cancer and how well it is responding to the APIs.
Chemotherapy APIs often concentrate in fast growing non-liver tissues, causing unpleasant side effects including reduced resistence to infection, nausea, sore mouth and hair loss.
Radiation therapy, often used in conjunction with chemotherapy or lesions above 5 cm, uses X-rays or other high-energy rays to kill cancer cells and shrink tumors. Radiation therapy often adds to chemotherapy side effects.
An electrolytic system that deposits cytotoxic medication with liver tissue has great potential to treat liver cancer, increasing survival rates and reducing side effects.
Electrolytic Alternatives to DC
Recognizing the risk and inefficiency of DC electrolytic treatments to tissue, devices using alternating current (AC) are often used for electrolytic treatment. However, because low frequency AC is accompanied by pain and causes muscle and nerve damage, AC can only be dispensed at higher frequencies.
Medically useful, and safe, high frequency AC has been determined as a current having a frequency of 10,000 or more cycles per second, thereby causing no muscular contractions and having no affect on nerves. In recognition of the damage caused by low frequency AC, regulatory agencies generally limit AC therapeutic modalities to high frequency AC above 10 MHz.
High frequency AC, though, is not useful for electrophoresis procedures because during oscillation, AC constantly changes polarity, causing cell membranes to block electrophoretic movement. The drawbacks of high frequency AC, therefore, limit its use to tissue treatments that require high temperatures. AC, for example, is used to generate heat for cutting tissue, cauterizing bleeding vessels and/or destroying unwanted tissue, including electro-epilation.
U.S. Patent Application published as U.S. 2001023330 teaches a transdermal AC iontophoresis assembly that dispenses pulsed AC frequencies below 100 Hz. However, to limit tissue damage, each pulse duration is less than 2 milliseconds, thereby reducing deposition and increasing treatment time similar to low voltage DC treatments.
U.S. Pat. No. 6,553,253 teaches electrokinetic delivery of therapeutic substances into tissue using AC rectified into DC at a frequency below 1 megahertz. Since this low frequency poses a danger of causing ventricle fibrillation, professional administration is required.
PCT patent application published as WO 2003/103522 teaches injecting a substance into a tissue and providing electrolytic treatments by using the injector as a first electrode in combination with a second remote electrode, similar to mono-polar electrosurgical system.
Articles, included by reference in their entirety, providing background for the present invention, include:
Rosemberg, Y. and Korenstein, R. “Incorporation of macromolecules into cells and vesicles by low electric fields: induction of endocytotic-like process” in Bioelchem. Biophys. Res. Comm. 1997, 42, 275-281
Antov Y, Barbul A, Mantsur H, and Korenstein R. “Electroendocytosis: exposure of cells to pulsed low electric fields enhances adsorption and uptake of macromolecules” in Biophysical Journal 2005, 88(3), 2206-2223.
Entin I, Plotnikov A, Korenstein R, Keisari Y. “Tumor growth retardation, cure, and induction of antitumor immunity in B16 melanoma-bearing mice by low electric field-enhanced chemotherapy” in Clinical Cancer Research 2003, 9(8), 3190-3197.
Nordenstrom B E. “Electrochemical treatment of cancer: Variable response to anodic and cathodic fields” American Journal of Clinical Oncology. 1989 December; 12 (6):530-6; as well as U.S. Pat. Nos. 4,289,135, 4,572,214 and 4,974,595 and China Patent 1042838 to Nordenstrom, et al.                Patents that provide background to the present invention include:        
U.S. Pat. No. 6,063,076, “Method and system for removal of hair” using electromagnetic energy to destroy hair matrix;
U.S. Pat. No. 4,155,363 “Electronically controlled apparatus for electrolytic depilation” using electric current that is interrupted between 1 to 3 seconds;
U.S. Pat. No. 5,443,441 “Apparatus and method for transdermal delivery of cosmetic compositions” uses electric current in a range of about 0.1 mA to about 10 mA;
U.S. Pat. No. 6,039,746 “Patch electrolysis system and method for removing hair from skin” applies an electrolysis current through patches secured to a skin surface;
European Patent EP 0824003 “Hair removal device and method” relies on iontophoretic deposition of thioglycolate depilatories;
PCT publication WO 2001/87171 “Method and System for Removal of Hair with a Conductive Layer” uses electromagnetic energy to destroy hair matrix;
European Patent EP 0783347 “Method of Hair Removal” by removing the hair and treating the exposed follicle to inhibit hair regeneration; and
In spite of the tremendous need and advantage for efficient and fast electrolytic treatment of tissue, there is no apparatus that provides electrolytic tissue treatment devoid of the above limitations.